Ashorn P, Englund G, Martin M A, Moss B, Berger E A
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Infect Dis. 1991 Apr;163(4):703-9. doi: 10.1093/infdis/163.4.703.
CD4(178)-PE40 is a recombinant protein consisting of a portion of human CD4 linked to active domains of Pseudomonas aeruginosa exotoxin A. In previous experiments with human T cell lines, the hybrid toxin was found to selectively kill cells infected with human immunodeficiency virus type 1 (HIV-1), and to inhibit HIV-1 spread in mixtures of infected and uninfected cells. CD4(178)-PE40 inhibits HIV-1 spread in cultured primary human lymphocytes. Moreover, the hybrid toxin selectively kills HIV-1 chronically infected monocyte/macrophage cell lines and inhibits HIV-1 spread in primary macrophage cultures. Control experiments indicate that the protective effects of CD4(178)-PE40 against HIV-1 spread are due to selective killing of the infected cells rather than simply to neutralization by the CD4 moiety. Thus, for the major cell types susceptible to HIV infection in vivo, surface envelope glycoprotein is expressed at sufficient levels to enable binding and internalization of CD4(178)-PE40 and consequent selective cell killing.
CD4(178)-PE40是一种重组蛋白，由人CD4的一部分与铜绿假单胞菌外毒素A的活性结构域相连组成。在先前用人T细胞系进行的实验中，发现这种杂交毒素能选择性杀死感染1型人类免疫缺陷病毒（HIV-1）的细胞，并抑制HIV-1在感染细胞与未感染细胞混合物中的传播。CD4(178)-PE40能抑制HIV-1在培养的原代人淋巴细胞中的传播。此外，这种杂交毒素能选择性杀死长期感染HIV-1的单核细胞/巨噬细胞系，并抑制HIV-1在原代巨噬细胞培养物中的传播。对照实验表明，CD4(178)-PE40对HIV-1传播的保护作用是由于选择性杀死感染细胞，而不仅仅是由CD4部分进行中和。因此，对于体内易受HIV感染的主要细胞类型，表面包膜糖蛋白表达水平足以使CD4(178)-PE40结合并内化，从而实现选择性细胞杀伤。
